title: A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia.
abstract: Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hardwick
authors.forename: Lee R
authors.initials: LR
authors.lastname: Machado
authors.forename: Luciana W
authors.initials: LW
authors.lastname: Zuccherato
authors.forename: Suzanne
authors.initials: S
authors.lastname: Antolinos
authors.forename: Yali
authors.initials: Y
authors.lastname: Xue
authors.forename: Nyambura
authors.initials: N
authors.lastname: Shawa
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Lilia
authors.initials: L
authors.lastname: Cabrera
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Paul
authors.initials: P
authors.lastname: Kelly
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona-Santos
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations / Q000235:genetics*; D019143:Evolution, Molecular; D005202:Asia, Eastern / Q000453:epidemiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005810:Multigene Family / Q000235:genetics; D009975:Orthomyxoviridae / Q000502:physiology; D002679:Pan troglodytes / Q000235:genetics; D058974:Phylogeography; D012641:Selection, Genetic / Q000235:genetics; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins